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Children (Basel, Switzerland) Mar 2024MIRAGE syndrome is a recently described congenital condition characterized genetically by heterozygous gain-of-function missense mutations in the growth repressor... (Review)
Review
MIRAGE syndrome is a recently described congenital condition characterized genetically by heterozygous gain-of-function missense mutations in the growth repressor sterile alpha domain containing 9 (SAMD9) located on the arm of chromosome 7 (7q21.2). The syndrome is rare and is usually diagnosed in newborns and children with myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy, hence the acronym MIRAGE. The aims of this paper are (1) to present fetal ultrasound features in a case where MIRAGE syndrome was diagnosed prenatally and (2) to review the existing literature records on prenatal manifestations of MIRAGE syndrome. In our case, the fetus had severe early fetal growth restriction (FGR) with normal Doppler studies, atypical genitalia, oligohydramnios, and hyperechogenic bowel at the routine mid-gestation anomaly scan. Amniocentesis excluded infections and numeric or structural chromosomal abnormalities while whole exome sequencing (WES) of the fetal genetic material identified the specific mutation. Targeted testing in parents was negative, suggesting the "de novo" mutation in the fetus. We could not identify other specific case reports in the literature on the prenatal diagnosis of MIRAGE syndrome. In cases reported in the literature where the diagnosis of MIRAGE syndrome was achieved postnatally, there are mentions related to the marked FGR on prenatal ultrasound. Severe early-onset FGR with no other apparent cause seems to be a central prenatal feature in these babies, and WES should be offered, especially if there are other structural abnormalities. Prenatal diagnosis of MIRAGE syndrome is possible, allowing for reproductive choices, improved counseling of parents, and better preparation of neonatal care.
PubMed: 38539345
DOI: 10.3390/children11030310 -
American Journal of Obstetrics and... Mar 2024Cytomegalovirus is responsible for the most common congenital infection, affecting 0.5% to 1.0% of live births in Europe. Congenital cytomegalovirus infection can be...
BACKGROUND
Cytomegalovirus is responsible for the most common congenital infection, affecting 0.5% to 1.0% of live births in Europe. Congenital cytomegalovirus infection can be diagnosed during pregnancy by viral DNA amplification in the amniotic fluid, but the prognosis of fetuses without severe brain abnormalities remains difficult to establish on the basis of prenatal imaging alone.
OBJECTIVE
To identify predictors of moderate to severe symptomatic cytomegalovirus infection among fetal blood parameters and to propose an algorithm on the basis of these parameters and on prenatal imaging that would provide the best positive and negative predictive values.
STUDY DESIGN
Fetal blood sampling at 21-28 weeks gestation was performed in fetuses with congenital cytomegalovirus infection confirmed by amniocentesis after maternal infection in the first-trimester or periconceptional period. We compared the levels of hemoglobin, thrombocytes, γ-glutamyl transpeptidase, aspartate aminotransferase, alanine aminotransferase, β2-microglobulin, immunoglobulins G and M, and cytomegalovirus DNA viral loads in amniotic fluid and fetal blood between those with moderate to severe symptomatic infection and those with asymptomatic to mild infection (median follow-up of 36 months for live births).
RESULTS
Among 58 fetuses included, 25 (43%) had a moderate to severe symptomatic infection: 16 with severe cerebral abnormalities, 5 with multiple signs or symptoms at birth, 2 with bilateral sensorineural hearing loss, and 2 with neurodevelopmental delay. The values of thrombocytes, aspartate aminotransferase, β2 microglobulin, Immunoglobulin M, and cytomegalovirus viral loads differed significantly between fetuses with moderate to severe symptomatic infection and those with asymptomatic to mild infection. The optimal strategy to predict moderate to severe symptomatic infection was to first perform fetal brain imaging, followed by fetal blood sampling with the following cutoffs: thrombocytes <120,000/mL, viremia ≥5 log/mL, and β2 microglobulin ≥12 mg/L). This recursive algorithm had a negative predictive value of 100% for moderately to severely symptomatic infection.
CONCLUSION
The combination of thrombocytes, β2-microglobulin, and cytomegalovirus viral load in fetal blood can be used for prognosis determination, particularly in cytomegalovirus-infected fetuses without severe brain abnormalities at the time of prenatal diagnosis. Future studies should evaluate whether these parameters remain useful in infected fetuses who have been treated with valacyclovir before fetal blood sampling.
PubMed: 38527603
DOI: 10.1016/j.ajog.2024.03.032 -
Acta Obstetricia Et Gynecologica... Jun 2024This study aimed to identify whether microbial invasion of the amniotic cavity and/or intra-amniotic inflammation in women with late preterm prelabor rupture of...
INTRODUCTION
This study aimed to identify whether microbial invasion of the amniotic cavity and/or intra-amniotic inflammation in women with late preterm prelabor rupture of membranes (PPROM) was associated with changes in concentrations of soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and its ratio in maternal serum, and whether placental features consistent with maternal vascular malperfusion further affect their concentrations.
MATERIAL AND METHODS
This historical study included 154 women with singleton pregnancies complicated by PPROM between gestational ages 34+0 and 36+6 weeks. Transabdominal amniocentesis was performed as part of standard clinical management to evaluate the intra-amniotic environment. Women were categorized into two subgroups based on the presence of microorganisms and/or their nucleic acids in amniotic fluid (determined by culturing and molecular biology method) and intra-amniotic inflammation (by amniotic fluid interleukin-6 concentration evaluation): (1) those with the presence of microorganisms and/or inflammation (at least one present) and (2) those with negative amniotic fluid for infection/inflammation (absence of both). Concentrations of sFlt-1 and PlGF were assessed using the Elecsys® sFlt-1 and Elecsys® PlGF immunoassays and converted into multiples of medians.
RESULTS
Women with the presence of microorganisms and/or inflammation in amniotic fluid had lower serum concentrations of sFlt-1 and sFlt-1/PlGF ratios and higher concentrations of PlGF compared with those with negative amniotic fluid. (sFlt-1: presence: median 1.0 multiples of the median (MoM), vs negative: median: 1.5 MoM, P = 0.003; PlGF: presence: median 0.7 MoM, vs negative: median 0.4 MoM, P = 0.02; sFlt-1/PlGF: presence: median 8.9 vs negative 25.0, P = 0.001). Higher serum concentrations of sFlt-1 and sFlt-1/PlGF ratios as well as lower concentrations of PlGF were found in the subsets of women with maternal vascular malperfusion than in those without maternal vascular malperfusion.
CONCLUSIONS
Among women experiencing late PPROM, angiogenic imbalance in maternal serum is primarily observed in those without both microbial invasion of the amniotic cavity and intra-amniotic inflammation. Additionally, there is an association between angiogenic imbalance and the presence of maternal vascular malperfusion.
Topics: Humans; Female; Pregnancy; Fetal Membranes, Premature Rupture; Amniotic Fluid; Adult; Placenta Growth Factor; Vascular Endothelial Growth Factor Receptor-1; Amniocentesis; Gestational Age; Chorioamnionitis; Biomarkers
PubMed: 38511515
DOI: 10.1111/aogs.14833 -
European Journal of Obstetrics,... May 2024This study aimed to determine the occurrence of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta, marked by elevated levels of...
Characterizing of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta marked by elevated amniotic fluid interferon gamma-induced protein 10 (IP-10) in pregnancies complicated by preterm prelabor rupture of membranes.
OBJECTIVES
This study aimed to determine the occurrence of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta, marked by elevated levels of interferon gamma-induced protein 10 (IP-10) (≥2200 pg/mL) in the amniotic fluid of women with preterm prelabor rupture of membranes (PPROM). Specifically, the study investigated whether these intra-amniotic inflammatory changes were more common in women with microbial invasion of amniotic cavity (MIAC) and intra-amniotic inflammation (IAI), as indicated by increased amniotic fluid interleukin (IL)-6 concentration (≥3000 pg/mL).
STUDY DESIGN
A cohort of 114 women with singleton pregnancies complicated by PPROM between 24 and 36 weeks of gestation were included. Amniotic fluid samples were obtained via amniocentesis upon admission. MIAC diagnosis involved aerobic and anaerobic cultures, as well as polymerase chain reaction (PCR) analysis of the amniotic fluid. Immunoassay tests and enzyme-linked immunosorbent assay (ELISA) were used to determine IL-6 and IP-10 concentrations, respectively.
RESULTS
Among the participants, 19.3 % and 15.8 % had MIAC and IAI, respectively. The occurrence of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta was similar between women with and without MIAC (25 % vs. 40.9 %, p = 0.136, adjusted p = 0.213). The rate of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta was significantly higher in women with IAI compared to those without, after adjusting for gestational age at sampling (55.6 % vs. 22.9 %, p = 0.005, adjusted p = 0.011).
CONCLUSION
This study revealed comparable rates of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta in women with and without MIAC, but a higher prevalence of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta in women with IAI. These findings suggest involvement of chronic inflammation even in women with PPROM with acute intra-amniotic inflammation.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Amniotic Fluid; Chorioamnionitis; Interferon-gamma; Chemokine CXCL10; Fetal Membranes, Premature Rupture; Inflammation; Placenta; Gestational Age
PubMed: 38503193
DOI: 10.1016/j.ejogrb.2024.03.006 -
Cureus Feb 2024Prenatal congenital inguinal hernia is a rare condition, with limited cases reported in the literature. Accurate prenatal diagnosis is crucial for appropriate management...
Prenatal congenital inguinal hernia is a rare condition, with limited cases reported in the literature. Accurate prenatal diagnosis is crucial for appropriate management and outcomes. We report a case of a 44-year-old woman at 36 weeks of gestation with well-controlled gestational diabetes diagnosed with prenatal congenital inguinal hernia. The patient's antenatal history included abnormal first-trimester screening tests for Down syndrome, but subsequent amniocentesis revealed no chromosomal abnormalities. Ultrasonography at 36 weeks showed an enlarged right scrotum with heterogeneous consistency and visible bowel peristaltic waves without signs of bowel obstruction, strangulation, or incarceration. At 39 weeks, oligohydramnios was diagnosed, leading to a decision for labor induction. However, the patient underwent a cesarean section upon her desire, giving birth to a male infant with congenital inguinal hernia. Both mother and child had a normal six-month postpartum follow-up. This case underscores the significance of detailed third-trimester ultrasonography in diagnosing prenatal congenital inguinal hernia. Early detection allows for better planning and management, highlighting the value of routine prenatal assessments for fetal organ status and early identification of malformations.
PubMed: 38500935
DOI: 10.7759/cureus.54356 -
Journal of Perinatology : Official... Mar 2024In this study, we aimed to evaluate BPA levels in the maternal serum and amniotic fluid of patients diagnosed with NTD. In addition, we wanted to investigate the...
OBJECTIVE
In this study, we aimed to evaluate BPA levels in the maternal serum and amniotic fluid of patients diagnosed with NTD. In addition, we wanted to investigate the relationship between neurodevelopmental defects, such as neural tube defects (NTD), and BPA levels.
STUDY DESIGN
This prospective observational study was carried out at Bursa Yüksek İhtisas Training and Research Hospital between April 15, 2021, and April 15, 2022. The study consisted of 92 patients between the ages of 18-45 who had an amniocentesis at 15-22 weeks of gestation. The patients were divided into two groups according to the indications of amniocentesis. Group 1 contained the patients with abnormal maternal serum screening results or cell-free DNA results and abnormal ultrasonography findings (45 patients). Group 2 contained the patients with a pre-diagnosis of NTD (47 patients). The first 5 cc fluids and maternal serum samples taken during the amniocentesis procedure of all patients were delivered to the biochemistry laboratory. The BPA values between groups were compared.
RESULTS
A statistically significant difference was found between the two groups in terms of amniotic fluid BPA levels (36.66 (19.00:82.00) and 39.62 (19.02-73.87)) and maternal blood BPA levels (22.26 (12.60-228) and 47.81 (12.89-228.39)). In cases with NTD, amniotic fluid BPA levels and maternal blood BPA levels were significantly higher than the control group. When AUC values were compared, the AFP numerical value was higher than the amniotic fluid and maternal blood BPA levels.
CONCLUSION
Plastic, which is indispensable for modern life, may negatively affect fetal development in intrauterine life. The data in this study says that high maternal blood BPA may be associated with NTD.
PubMed: 38499756
DOI: 10.1038/s41372-024-01925-3 -
Prenatal Diagnosis Mar 2024This study aimed to develop and validate a prenatal cell-free DNA (cfDNA) screening method that uses capture-based enrichment to genotype fetal autosomal recessive...
OBJECTIVE
This study aimed to develop and validate a prenatal cell-free DNA (cfDNA) screening method that uses capture-based enrichment to genotype fetal autosomal recessive disorders. This method was applied in pregnancies at high risk of autosomal recessive non-syndromic hearing loss (ARNSHL) to assess its accuracy and effectiveness.
METHODS
This assay measured the allele counts in both white blood cell DNA and cfDNA from the blood samples of pregnant women using a capture-based next-generation sequencing method. It then applied a binomial model to infer the fetal genotypes with the maximum likelihood. Ninety-four pregnant couples that were carriers of variants of ARNSHL in GJB2 or SLC26A4 were enrolled. The fetal genotypes deduced using this screening method were compared with the results of genetic diagnosis using amniocentesis.
RESULTS
Of the 94 couples, 65 carried more than one variant, resulting in 170 single-nucleotide polymorphism (SNP) loci to be inferred in the fetuses. Of the 170 fetal SNP genotypes, 150 (88.2%) had high confidence calls and 139 (92.7%) of these matched the genotypes obtained by amniocentesis result. Out of the remaining 20 (11.8%) cases with low-confidence calls, only 14 (70.0%) were concordant with genetic diagnosis using amniocentesis. The concordance rate was 100% for sites where the maternal genotype was wild-type homozygous. The discordance was site-biased, with each locus showing a consistent direction of discordance. Genetic diagnosis identified a total of 19 wild-type homozygotes, 46 heterozygotes, 19 compound heterozygotes, and 10 pathogenic homozygotes. This screening method correctly genotyped 81.9% (77/94) of fetuses and demonstrated a sensitivity of 89.7% and a specificity of 89.2% for correctly identifying ARNSHL.
CONCLUSION
This capture-based method of prenatal screening by cfDNA demonstrated strong potential for fetal genotyping of autosomal recessive disorders.
PubMed: 38488843
DOI: 10.1002/pd.6550 -
Taiwanese Journal of Obstetrics &... Mar 2024
Topics: Pregnancy; Female; Humans; Cri-du-Chat Syndrome; Chromosomes, Human, Pair 5; Prenatal Diagnosis; Chromosome Aberrations; Cytogenetic Analysis; Fetus; Chromosome Deletion; Amniocentesis
PubMed: 38485330
DOI: 10.1016/j.tjog.2024.01.029 -
Taiwanese Journal of Obstetrics &... Mar 2024We present incidental detection of familial 8p23.2 microduplication encompassing CSMD1 associated with mosaic 46,XY,t(7;8)(q31.2;p23.1)/46,XY at amniocentesis in a...
Incidental detection of familial 8p23.2 microduplication encompassing CSMD1 associated with mosaic 46,XY,t(7;8)(q31.2;p23.1)/46,XY at amniocentesis in a pregnancy with no apparent phenotypic abnormality and a favorable outcome.
OBJECTIVE
We present incidental detection of familial 8p23.2 microduplication encompassing CSMD1 associated with mosaic 46,XY,t(7;8)(q31.2;p23.1)/46,XY at amniocentesis in a pregnancy with no apparent phenotypic abnormality and a favorable outcome.
CASE REPORT
A 38-year-old, gravida 2, para 1, phenotypically normal woman underwent amniocentesis at 19 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY,t(7;8)(q31.2;p23.1)[2]/46,XY[20]. The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes and parental bloods revealed the result of a 2.178-Mb 8p23.2 microduplication encompassing CSMD1, or arr 8p23.2 (3,070,237-5,248,586) × 3.0 [GRCh37 (hg19)] in the fetus and the mother. The father did not have such a microduplicaiton. Prenatal ultrasound findings were unremarkable. At 38 weeks of gestation, a 2880-g phenotypically normal male baby was delivered. All the cord blood, umbilical cord and placenta had the karyotype of 46.XY. When follow-up at age six months, the neonate was normal in phenotype and development.
CONCLUSION
Mosaicism for a balanced reciprocal translocation with a euploid cell line can be a transient and benign condition. Familial 8p23.2 microduplication encompassing CSMD1 can be associated with a favorable outcome.
Topics: Pregnancy; Infant, Newborn; Female; Male; Humans; Infant; Adult; Amniocentesis; Comparative Genomic Hybridization; Karyotyping; Karyotype; Mosaicism; Trisomy; Membrane Proteins; Tumor Suppressor Proteins
PubMed: 38485324
DOI: 10.1016/j.tjog.2024.01.023 -
Frontiers in Genetics 2024
PubMed: 38482384
DOI: 10.3389/fgene.2024.1371166